Treatment of multiple sclerosis with oxytocin



United States Patent 3,274,060 TREATMENT OF MULTIPLE SCLEROSIS WITHOXYTOCIN Charles D. Bossinger, Kankakee, Ill., assiguor t0 ArmourPharmaceutical Company, Chicago, 11]., a corporation of Delaware NoDrawing. Filed May 23, 1962, Ser. No. 196,882

8 Claims. (Cl. 167-74) This invention relates to treatment of multiplesclerosis with oxytocin, and more particularly to the administration ofhormonal substances consisting predominantly of oxytocin for thealleviation of multiple sclerosis.

Multiple sclerosis is a chronic progressive disease affecting thecentral nervous system, characterized by exacerbations and remissions,and pathologically involving multiple patches of sclerosis scatteredthroughout the central nervous system in which there may bedisintegration of the myelin sheet and preservation of the accesscylinder in the midst of extensive patches of sclerosis. The patientafllicted with multiple scleroisis may early undergo symptom-ireeperiods between episodes of symptomatology until the gradualdisintegration of the access cylinders produces permanent centralnervous system impairment.

It is believed that the pathological features represent a generalcentral nervous system response to a variety of etiological agents.There is as yet no specific therapy for multiple sclerosis, but thereare available numerous techniques for providing temporary allevation ofsymptoms in patients afflicted with multiple sclerosis.

A primary object of the invention is to provide for the alleviation ofmultiple sclerosis through the administration of a substance consistingpredominantly of oxytocin. A further object is to provide for thealleviation of multiple sclerosis or for the arresting or delaying ofthe course of the disease through the administration to human beingsafi'licted with mulitiple sclerosis of oxytocin. Other specific objectsand advantages will appear as the specification proceeds.

Oxytocin is the hormone of the posterior pituitary or neurohypophysiswhich has hitherto been employed primarily to stimulate parturition onthe basis of its action in enhancing uterine contractions. The drug hasbeen available for a number of years as a semi-purified preparationcontaining vas-opressor and anti-diuretic activity (vasopressin). Also,oxytocin, as well as vasopressin, has recently been synthesized by DuVigneaud.

In one embodiment of the invention, oxytocin is administered to thepatient affiicted with multiple sclerosis over periods of time, whichtogether with the dosage will be determined largely by the condition ofthe patient, the severity of systems, and the status of the disease inthe patient at the time of treatment; that is, the dosage and plan oftreatment with oxytocin will be determined by the physician at the timeof instituting treatment. However, it may be stated generally thatalleviation of multiple sclerosis may be obtained with conventionaloxytocin preparations of te fast-acting type with about to 100 USP unitsthereof administered about every 1 2 hours. The drug may be administeredparenterally, especially intramuscularly or subcutaneously, or byinsufilation, etc. In administering the drug by injection, any suitablevehicle, such as Water, saline, aqueous gelatin, etc, may be employed.Also, long-acting preparations may be used so that the injections may berequired only once a day or several times a week during the period oftreatment.

The treatment may be required only during periods in which there isexacerbation of the disease process in the afflicted patient or, ifdesired, treatment may be continued with oxytocin during periods ofremission. It will also be apparent that due to the unknown and variedetiology of the disease, and because of the vicissitudes of making adiagnosis of this condition, not all patients in whom there is theimpression of afi liction with multiple sclerosis, will be expected tobenefit by the treatment of this invention. However, those patients whowill respond to this treatment may be readily determined by trialtherapy. i

The treatment will be further illustrated by the following examples.

EXAMPLE 1 Patients afflicted with multiple sclerosis were treated withvarious dosages of oxytocin administered subcutaneously in aqueousgelatin.

Before setting out the results obtained, it is necessary to indicate themethod of determining or scoring the results obtained.

Considerable difiiculty has heretofore been experienced in the treatingof multiple sclerosis because of the frequently noted discrepancybetween the extent of recovery of individual signs and symptoms (e.g.,reflexes, strength, etc), and the degree of change in the overalldisability status (as expressed strikingly by the quality of locomotion,as well as by the ability to carry out other complicated tasks). Aftertrial and error, a weighting system and resulting scoring method havebeen finally arrived at which appear to reflect adequately the state ofthe disease and its fluctuations in individual patients. It is comprisedof score values assigned to 50 significant variables of the disease,weighted according to the importance of the variable. Normal findingsare given a score of zero, while varying degrees of neurologic involvement are weighted from 1 to -I20. Thus, high score values are givento signs of relatively great heuristic value, while relatively lowscores are assigned to items which either are less important ormeaningful or are not necessarily representative of the organic state,being instead subject to fluctuations of emotion, energy level, ormotivation. Using this method, a patient without neurologicabnormalities would receive a score of zero, while the maximum score ofa totally disabled patient ranges down to a 500 points. Such a weightingchart was employed in the evaluation of the results obtained by theadministration of oxytocin to patients inflicted with multiple sclerosisin accordance with this invention. By and large the results were mostpromising.

A detailed account of this scoring system, which was developed by Dr.Leo Alexander of the Boston State Hospital, Boston, Mass, is reported inthe Quarterly Review of Pediatrics, vol. 7, No. 2, May 1952, pages82-84, inclusive, under the title, Quantitative Aspects of theNeurological Examination as a Means of Evaluating Improvement in ChronicDisease of the Nervous System. The weighting chart employed in our testsis set out below:

Weighting chart Vision:

Corrected-- Less than 20/20 20 20/200-2/100 15 20/70-20/50 1O20/40-20/25 Pupils:

Pupillary asymmetry 2 Abnormal reaction to light or accommodation 5 Eyemovements:

Marked (such as eye muscle palsies, diplopia) Moderate or slight (suchas disturbance of convergence) 5 Nystagmus 5 Tonguedeviation 2 Facials:

Asymmetry- Marked 5 Slight 3 Optic discs:

Pallor Marked Moderate 10 Minimal or slight 5 Blurring 10 Visual fields:

Restricted- Marked 15 Moderate 10 Minimal or slight 5 Scotoma (not to bescored if vision is less than /200) 10 Speech:

Defect-- Marked 15 Moderate 10 Minimal or slight 5 Posture:

Inability to stand 15 Abnormal- Marked 10 Slight 5 Status:

Bedridden 20 Wheel chair 15 Walking with support of other person 10Crutches 8 Cane 7 Walking unaided with abnormal gait 5 Coordination:

Disturbance Marked 10 Moderate 5 Minimal or slight 2 Adiadochokinesis: 5Slight or i- 2 Romberg: 10 :L 5 Strength Paralysis 20 Weakness- Marked15 Moderate 10 Slight 5 Tonus 3 (increased or decreased):

Marked 15 Moderate 10 Slight 5 Abnormal movements:

Marked 10 Moderate 5 Slight 2 Tendon reflexes:

Absent 2 Clonus:

3 Mayer 0 2 Hoflman:

i 3 Abdominals (per side):

Absent 15 Partially preserved 10 Exhaustible 5 Cremasterics-- (perside):

Absent 15 i 10 Babinski( per side):

i 10 Absent plantar reflex without Babinski 5 Other abnormal toephenomena:

Each 5 Sphincters:

Incontinence 20 Geo. incontinence 10 Retention 10 Frequency 5 Urgency 5Difficulty in starting stream-- occasional retention 5 Sensationpersideper quality:

Absent l0 Diminished 5 Hyperesthesia or focal pain 10 Paresthesia orsubjective numbness 5 Impotence 15 Other significant signs 10 Such as:

Exophthalmus due to retrobulbar neuritis with pain of eyeball.

Temperature differences. Paravertebral spasm, etc.

Disturbances of coordination are scored as follows: One combined scoreis given for ataxia, intentional tremor and dysmetria, but a separatescore for each arm and leg, and a separate score for performance witheyes closed and for per formance with eyes opened; 1.e., forfinger-to-nose test, fingerto-object test, knee-to-heel test, and fortoe-to-object test. One combined score for each side is given forbradyteleokinesis, one for static tremor, and one for tremor at rest.

2 Strength is scored for extension and flexion of each important groupof muscles separately. The following groups are distinguished: hip,knee, foot shoulder, elbow and grip of hand (together with Wrist-noseparate score for wrist). Thus a complete triple fiexion paralysis ofthe leg would be scored 60 moderate weakness of extension of one hip 10;or marked weakness of grip on one hand 15 01' slight Weakness ofextension of one Wrist 5.

3 Tonusscore per extremity.

Of twenty-one patients treated in accordance with this invention, twelveshowed immediate improvement by raising their scores from 3-50 points,three raised their scores from 50-100 points, three raised their scoresmore than points, and only three showed either no improvement orregression. It should be borne in mind that a change of score from 300to 200, for example, represents a raise in score of 100 points.

In the treatment for multiple sclerosis, the hormone substanceadministered to the patient preferably consists predominantly ofoxytocin, and best results have been obtained Where the oxytocin issubstantially free from anterior pituitary hormones. The oxytocin may beadministered in various vehicles, as above described, and

may also be supplemented by other substances which give long-actingresults, etc., and such vehicles or addition preparations may beutilized for their well-known advantages and functions.

While in the foregoing specification I have set forth specificpreparation ingredients and procedures in considerable detail for thepurpose of illustrating embodiments of the invention, it will beunderstood that such details may be varied by those skilled in the artwithout departing from the spirit of my invention.

I claim:

1. In treatment for multiple sclerosis, the parenteral administration toa human being afflicted with multiple sclerosis of a hormone substanceconsisting predominantly of oXytocin said hormone substance containingsufiicient oxytocin to provide said human being with at least from about5 to about 100 USP units of oxytocin per 12 hours.

2.. In treatment for multiple sclerosis, the parenteral administrationto a human being being afiiicted With multipule sclerosis of oXytocin inan amount suflicient to provide at least about 5 USP units of oxytocinper 12 hours of treatment.

3. The method of treatment for multiple sclerosis comprisingadministering parenterally to a human being afilicted with multiplesclerosis at least an effective amount of a hormone substance consistingessentially of oxytocin.

4. The method of treatment for multiple sclerosis comprisingadministering by insuffiation to a human being afllicted with multiplesclerosis at least an effective amount of a hormone substance consistingessentially of oxytocin.

5. The method according to claim 3 in which said hormone substance issubstantially free from anterior pituitary hormones.

6. The method according to claim 4 in which said hormone substance issubstantially free from anterior pituitary hormones.

7. The method of treatment for multiple sclerosis comprisingadministering parenterally to a human being afflicted with multiplesclerosis a dose containing at least from about 5 to about USP units ofoxytocin per 12 hours of treatment and a non-toxic pharmaceuticallyacceptable excipient.

8. The method of treatment for multiple sclerosis comprisingadministering by insufflation to a human being afflicted With multiplesclerosis a dose containing at least from about 5 to about 100 USP unitsof oxytocin per 12 hours of treatment and a non-toxic pharmaceuticallyacceptable excipient.

No references cited.

JULIAN S. LEVITI, Primary Examiner. FRANK CACCIAPAGLIA, JR., Examiner.LEROY B. RANDALL, Assistant Examiner.

1. IN TREATMENT FOR MULTIPLE SCLEROSIS, THE PARENTERAL ADMINISTRATION TO A HUMAN BEING AFFLICTED WITH MULTIPLE SCLEROSIS OF A HORMONE SUBSTANCE CONSISTING PREDOMINANTLY OF OXYTOCIN SAID HORMONE SUBSTANCE CONTAINING SUFFICIENT OXYTOCIN TO PROVIDE SAID HUMAN BEING WITH AT LEAST FROM ABOUT 5 TO ABOUT 100 USP UNITS OF OXYTOCIN PER 12 HOURS. 